MSCA-DN PhD in oligodendrocyte-targeted gene therapy PMLD; Nicosia, Cyprus

Would you like to contribute to the development of gene therapies for rare neurological diseases? Join POLARIS and develop innovative human cell and animal models to investigate gene therapy for Pelizaeus-Merzbacher-like disease.

POLARIS is a European Marie Skłodowska-Curie Doctoral Network focused on accelerating therapy development for leukodystrophies: rare genetic disorders affecting the brain's white matter. The network aims to strengthen the full translational pathway, from understanding disease mechanisms and developing disease models to preclinical therapy testing, clinical readiness and patient-informed treatment priorities.

To achieve this, POLARIS brings together expertise in leukodystrophy biology, advanced disease models, therapeutic innovation, biomarker development, clinical translation, patient engagement, and ethical, regulatory and health-economic aspects of therapy development. The network will train a cohort of doctoral candidates in an international and interdisciplinary environment, combining academic research, industry-based preclinical development, secondments, network-wide training and transferable-skills development.

For this position, the recruiting organisation is the Cyprus Institute of Neurology & Genetics (CING) in Nicosia, Cyprus. CING will employ you and you will be embedded in the POLARIS consortium. Academic supervision and disease-specific expertise will be provided by Prof Kleopa Kleopa and Dr Irene Sargiannidou from the Neuroscience Department.

This doctoral project focuses on establishing isogenic iPSC-derived myelinating organoids as a physiologically relevant human in vitro model of Pelizaeus-Merzbacher-like disease type 1 (PMLD1).

You will first test leading AAV capsids developed by Myrtelle Therapeutics Inc. in the in vitro model. You will assess their effects on myelination and oligodendrocyte survival. The most promising oligodendrocyte-targeting AAV variants will subsequently be tested in a PMLD1 mouse model to determine their therapeutic potential in vivo.

The project requires a strong foundation in neuroscience and an interest in both stem cell-based and animal research. Prior experience with cell culture techniques, behavioural and neurological phenotyping, and handling mice is an advantage.

Planned secondments will provide specialised training in establishing isogenic iPSC-derived myelinating organoids under the supervision of Dr Hendrick Rosewich in Tübingen, Germany. You will also have the opportunity to develop experience in patient advocacy, networking and research planning through a placement at the European Leukodystrophy Association (ELA).

The position is based in Nicosia, Cyprus, with academic enrolment through the Graduate School of the Cyprus Institute of Neurology and Genetics. You will pursue a PhD degree in Neuroscience.

You will contribute to the development and evaluation of gene therapy approaches for PMLD
1. Your work includes:

• establishing and using isogenic iPSC-derived myelinating organoids as a human in vitro disease model;
• testing AAV variants and assessing their effects on myelination and oligodendrocyte survival;
• using a PMLD1 mouse model to evaluate the therapeutic potential of selected AAV variants in vivo;
• applying behavioural and neurological phenotyping and other experimental approaches to assess disease mechanisms and treatment responses;
• analysing and interpreting experimental results and collaborating with researchers at CING and across the POLARIS consortium.

You will also participate in the POLARIS network-wide training programme and planned secondments. This gives you the opportunity to develop scientific and transferable skills in an international research environment.

We are looking for a candidate with a Master's degree in Life Sciences, preferably in Neuroscience, and a strong interest in translational neuroscience and rare disease research.

Relevant experience may have been gained during an internship, thesis project or other research project. We are looking for:

• hands-on experience with in vivo mouse research;
• experience with behavioural or neurological phenotyping is an advantage;
• knowledge of animal welfare regulations and ethical principles, and an understanding of rigorous experimental design;
• a careful and reproducible approach, with strong analytical and problem-solving skills;
• good written and verbal communication skills and the ability to collaborate in an interdisciplinary and international research…